The object of the proposed investigation is to study the mechanism by which the presence of the spleen is required for the progressive growth of a spontaneous B cell leukemia (BCL1) in BALB/c mice. Our preliminary date show that the intraperitoneal injection of BCL1 cells into normal BALB/c mice produces a marked progressive lymphocytosis and uniform mortalty within 8-12 weeks. Splenectomy prior to injection of tumor cells or before marked leukocytosis results in a stable low white blood cell count which does not increase over a period of at least 5 months and is associated with little if any mortality. Transfer of white blood cells from the latter recipients to normal (non-splenectomized) mice produces progressive tumor growth and death. Splenectomy after marked lymphocytosis produces a transient decrease in the lymphocytosis, but progressive tumor growth ensues. We will attempt to determine the cellular and/or humoral basis of the interaction between the tumor and the spleen by adding back whole spleen fragments, dissociated spleen cells, separated into T cells, B cells, macrophages, null cells, etc., spleen fragments in millipore chambers to splenectomized recipients of tumor cells with a stable white blood cell count. Any of the latter procedures which induce progressive tumor growth will help elucidate the nature of the interaction. Therapeutic trials will also be performed to examine the efficicacy of late splenectomy and x-irradiation or cyclophosphamide in recipients with progressive tumor growth. We will also examine the effect of LPS treatment in vitro on subsequent tumor growth in vivo, since the BCL1 cell is unique in that it proliferates and secretes immunoglobulin in vitro in response to this mitogen.